[HTML][HTML] IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2+Vγ6+γδ T cells

A Akitsu, H Ishigame, S Kakuta, S Chung… - Nature …, 2015 - nature.com
A Akitsu, H Ishigame, S Kakuta, S Chung, S Ikeda, K Shimizu, S Kubo, Y Liu, M Umemura…
Nature communications, 2015nature.com
Abstract Interleukin-17 (IL-17)-producing γδ T (γδ17) cells have been implicated in
inflammatory diseases, but the underlying pathogenic mechanisms remain unclear. Here,
we show that both CD4+ and γδ17 cells are required for the development of autoimmune
arthritis in IL-1 receptor antagonist (IL-1Ra)-deficient mice. Specifically, activated CD4+ T
cells direct γδ T-cell infiltration by inducing CCL2 expression in joints. Furthermore, IL-17
reporter mice reveal that the Vγ6+ subset of CCR2+ γδ T cells preferentially produces IL-17 …
Abstract
Interleukin-17 (IL-17)-producing γδ T (γδ17) cells have been implicated in inflammatory diseases, but the underlying pathogenic mechanisms remain unclear. Here, we show that both CD4+ and γδ17 cells are required for the development of autoimmune arthritis in IL-1 receptor antagonist (IL-1Ra)-deficient mice. Specifically, activated CD4+ T cells direct γδ T-cell infiltration by inducing CCL2 expression in joints. Furthermore, IL-17 reporter mice reveal that the Vγ6+ subset of CCR2+ γδ T cells preferentially produces IL-17 in inflamed joints. Importantly, because IL-1Ra normally suppresses IL-1R expression on γδ T cells, IL-1Ra-deficient mice exhibit elevated IL-1R expression on Vγ6+ cells, which play a critical role in inducing them to produce IL-17. Our findings demonstrate a pathogenic mechanism in which adaptive and innate immunity induce an autoimmune disease in a coordinated manner.
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